Recently, bone-loss is often caused by a disease or a car accident, so that supplementing bone-loss is importantly required. Bone-transplantation is one way to supplement bone-loss and more preferably bone-filling composition is used. Bone-extension technique is performed today to extend one's height in stature or to correct undersized jaws, for which bone-filling composition is also required a lot.
Bone-extension technique is to stimulate bone-growth, especially growth in height, by stretching based on the theory that “Tension forces stimulate histogenesis”. Bone-extension technique was first devised for the growth of limb bones but has been widely used for jawbone extension. Jawbone extension method is one of techniques performed in the field of cranial jaw facial surgery, which can improve facial ratio not by cutting bone but by moving facial bones gradually by fixing bone-stretching apparatus to retreated parts of jawbone and central facial form.
Bone-extension technique has been successfully used for supplementing the loss of long bone since Ilizarov found out biomechanical elements for bone-extension (Ilizarov G A, J. Dis. Orthop. Inst., 48(1): 1, 1988; Ilizarov G A, Clin. Ortho., 239: 263, 1989; Ilizarov G A, Clin. Ortho., 238: 249, 1989) . It is important for performing the successful bone-extension to keep blood circulation in the part of bone-extension and to fix external fixator stably to both sides of joint part of cortical bone, resulting in the stimulation of bone-consolidation by gradual extension of bone (White S H, J. Bone Join Surgery, 72-B: 350, 1990; White S H, Orthop. Clin. North. Amer., 22: 569, 1991; Fishgrund J., Paley D., Sulter D., Clin. Orthop., 301: 31, 1994).
The period of bone-consolidation depends on extension part of bones such as facial bone or long bone, blood circulation condition, the age of a patient, etc. Bone-consolidation of craniofacial bone takes 3-5 weeks for children and 6-12 weeks for adults after bone-extension, while it takes 3-6 months in long bone regardless of age. Performing bone-extension for craniofacial bone has a couple of problems; one is carrying high possibility of complications and the other is postponing the return to normal life due to the long bone-consolidation time. Precisely, the treatment after bone-extension takes 2-4 months composing of latent phase, bone-extension phase and bon-consolidation phase.
According to Charls and Sailer's report, extending 1 mm a day shows stronger biochemical and physiological characteristics than extending 2-3 mm a day (Carls & Sailer, J. Craniomaxillofac Surg., 94: 152, 1994). Ilizarov has also reported that extending 1 a day showed best results while extending 0.5 mm a day caused premature bone-consolidation and extending 2 mm a day caused undesirable changes in extended tissues (Ilizarov, J. Dis. Orthop. Inst., 48(1): 1, 1988; Ilizarov, Clin. Ortho 239: 263, 1989). In addition, it has also been known that consecutive extending causes the least damage in tissues but the best development of capillary vessels and bone-formation. Therefore, shortening the period of bone-extension and bone-consolidation can contribute to prevent possible complications and to make a patient return to normal life early. In order to shorten the period of bone-extension and bone-consolidation, bone-filling composition is used to stimulate bone-formation and bone-consolidation.
Meanwhile, autobone-graft, treated homograft, heterograft and bone graft substitute have been known to stimulate bone-formation. Autobone-graft is used for the treatment of joint-agglutination or non-agglutinational fracture, or for avoiding damage and void caused by infection, tumor and operation by supplementing bone cavity or bone loss. Transplanted autobone is adsorbed well, resulting in re-circulation of blood. At this time, osteoprogenitor cells are differentiated to bony osteogenesis cells and the activation thereof stimulates bone-regeneration as well as treats bone-loss. However, autobone-graft has problems such as limitation in the amount of extraction and high morbidity caused by the secondary operation for the part of donation. Thus, bone morphogenic protein or other bone-grafting substitute is used to induce bone-regeneration at extended sites. Bone morphogenic protein is regarded as the strongest bone-inducing material but is limited in clinical use because it is very expensive and hard to obtain.
Calcium sulfate is a kind of bone-filling material that is suitable for human body and induces the growth of bony osteogenesis cells and blood vessels as well as stimulates bone-consolidation in the early stage. This material is contribute to construct a normal bone structure by stimulating new bone-formation in a proper condition, plays as a defense shield during bone-healing by preventing the growth of unnecessary connecting tissues and can be substituted with bone during the recovery process. Beeson confirmed by the experiment with dogs that calcium sulfate injected into frontal sinus of dogs induced bone-regeneration within 4-6 weeks (Beeson W., Arch Otolaryngol, 107: 664, 1981), and Pecora et al. also reported bone-healing effect of calcium sulfate injected into bone-loss area of mouse jawbone that was observed partly or over the whole area three weeks after injection (Pecora G., Andreana S., Margarone III J E., Covani U., Sottosanti J S., Oral Surg. Oral Med. Oral Pathol. Oral Radio Endod., 84: 434, 1997). According to Pelter's report, calcium sulfate was safe to be administered to various types of bone-loss patients, stimulated bone-regeneration as being absorbed in a body within several weeks or several months and did not cause any complication or any danger (Pelter L F., Am. J. Surg., 97(3): 311, 1959). However, the conventional calcium sulfate used as a bone-filling composition for bone-regeneration is difficult to be injected in bone-loss area because the composition is in a form of tablets or powder. In order to inject that composition, operation with a scar is unavoidable, which suffers patients.
Thus, the present inventors have tried to improve the way to administer calcium sulfate. As a result, the present inventors prepared a gel type composition containing calcium sulfate and viscous polymer, and accomplished the present invention by confirming that the composition of the invention can easily be administered into the bone-loss area by injection, does not diffuse to surrounding organs and shortens the bone-consolidation period by stimulating bone-formation and bone-consolidation.